A variety of surgical procedures and medical devices are currently used to relieve intraluminal constrictions caused by disease or tissue trauma. An example of one such procedure is percutaneous transluminal coronary angioplasty (PTCA). PTCA is a catheter-based technique whereby a balloon catheter is inserted into a blocked or narrowed coronary lumen of the patient. Once the balloon is positioned at the blocked lumen or target site, the balloon is inflated causing dilation of the lumen. The balloon is deflated and the catheter is then removed from the target site and the patient's lumen, thereby allowing blood to freely flow through the unrestricted lumen.
Although PTCA and related procedures aid in alleviating intraluminal constrictions, such constrictions or blockages reoccur in many cases. The cause of these recurring obstructions, termed restenosis, is due to the body responding to the surgical procedure. Restenosis of the artery commonly develops over several months after the procedure, which may require another angioplasty procedure or a surgical by-pass operation. Proliferation and migration of smooth muscle cells (SMC) from the media layer of the lumen to the intima cause an excessive production of extra cellular matrices (ECM). This production is believed to be one of the leading contributors to the development of restenosis. Extensive tissue thickening of tissues narrows the lumen of the blood vessel, constricting or blocking the blood flow through the vessel.
Stents, synthetic vascular grafts or drug therapies, either alone or in combination with the PTCA procedure, are often used to reduce, or in some cases eliminate, the incidence of restenosis. The term “drug(s),” as used herein, refers to all therapeutic agents, diagnostic agents/reagents and other similar chemical/biological agents, including combinations thereof, used to treat and/or diagnose restenosis, thrombosis and related conditions. Examples of various drugs or agents commonly used include heparin, hirudin, antithrombogenic agents, steroids, ibuprofen, antimicrobials, antibiotics, tissue plasma activators, monoclonal antibodies, and antifibrosis agents.
Since the drugs are applied systemically to the patient, they are absorbed not only by the tissues at the target site, but by all areas of the body. As such, one drawback associated with the systemic application of drugs is that areas of the body not needing treatment are also affected. To provide more site-specific treatment, balloon catheters are frequently used as a means of delivering the drugs exclusively to the target site. The balloon assembly of the balloon catheter is positioned at the target site and inflated to compress against the arteriosclerosis and remodel the walls of the artery. The therapeutic agent can then administered directly to the target site through small holes or apertures in the wall of the balloon assembly. The apertures through the balloon may be formed by mechanical punching, mechanical drilling, directing a laser beam at the elastic material, directing an ion beam at the elastic material, or directing an electron beam at the elastic material, among other possibilities.
Apertures formed in the walls of the balloon assembly offer many advantages to potential users. However, such devices may be deficient in their drug delivery characteristics. For example, when the balloon is filled with therapeutic or diagnostic liquids/fluids under relatively high pressure, fluid is ejected from the apertures in the form of a jet-like flow. The fluid jetting from the apertures is at such a velocity so as to cause tissue damage to the lumen or vessel wall. Since the rate at which the drug is released or delivered to the target site is a function of the structural properties of the apertures, drug release rates are inadequately controlled. As such, the balloon configuration greatly limits the usefulness of the catheter.
Another way of delivering a drug by a balloon is to coat the balloon with or without apertures with a coating having a drug. The coating can be a polymer which contains the drug or a polymer-free drug coating. The inflation of the balloon “squeezes” the coating against the target lesion, administering the drug locally immediately prior to and upon impact. The use of a polymer to contain the drug is beneficial in that the polymer prevents premature release of the drug from the balloon. Preventing premature release of the drug from the balloon means that a dosage of the drug is maintained on the balloon so that a therapeutically effective amount of the drug can be applied to the target lesion upon balloon inflation. The detriment in using a polymeric coating on the balloon, on the other hand, is that the polymer may prevent an adequate release of the drug at the target site during and subsequent to the inflation of the balloon. The window of opportunity for application of a drug by a balloon is very short. A physician positions the balloon at the target region, inflates the balloon, deflates it and then removes it. The application of the drug should only occur during that time period for local, concentrated administration. Preferably, most if not all of the drug should be applied during inflation of the balloon and when there is contact between the balloon and the lumen. A polymeric coating may not allow for the drug to elute or be release from the coating quickly enough. Accordingly, what is needed is a polymeric coating that allows for quick or a burst release of the drug from a balloon during a very short window of opportunity.
This invention provides for a novel drug coating for a balloon. This invention also provides for a novel method of making coatings including a drug for a balloon.